Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus.

We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.

Mineralocorticoid receptor p.I180V polymorphism: association with body mass index and LDL-cholesterol levels.

BACKGROUND/AIMS: Aldosterone and the mineralocorticoid receptor (MR) play a major role in sodium balance and blood pressure control. They are also involved in adipocyte metabolism. The aim of this study was to analyze the association between the MR p.I180V polymorphism with hypertension and markers of cardiovascular risk. DESIGN AND METHODS: Case-control study nested within a cohort of 2063 subjects followed since birth to date. All subjects (age 23-25 yr old) from the entire cohort with systolic and diastolic hypertension (no.=126) were paired with 398 normotensive controls. MR p.I180V genotype association with anthropometric and biochemical markers of cardiometabolic risk was tested. RESULTS: There was a significant association of the MR p.I180V genotype with body mass index (BMI) and LDL-cholesterol level (p<0.01). Hypertensive subjects carrying the polymorphic G allele (AG or GG genotypes) presented significantly higher BMI (30.0+/-6.0 vs 28.7+/-5.6 kg/m(2); p<0.01) and higher LDL-cholesterol (139.9+/-60.3 vs 109.9+/-35.5 mg/dl; p<0.01). The frequency of the polymorphism MR p.I180V was similar between hypertensive subjects and controls (p=0.15). CONCLUSIONS: The MR p.I180V polymorphism seems to be associated with cardiovascular risk factors including BMI and LDL-cholesterol levels. This original in vivo finding reinforces the role of MR in adipocyte biology and in cardiovascular disease.

Parathyroid hormone secretion in women in late menopause submitted to EDTA-induced hypocalcemia.

OBJECTIVE: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans has not been fully defined. The main objective of the present study was to evaluate basal and EDTA-stimulated PTH levels in young women (Group Y=30.9 years, N=7) and in women in late menopause (Group M=64.7 years, N=7) and their relationship to bone mineral density. METHODS: The PTH secretion test was performed by induction of hypocalcemia through intravenous administration of EDTA for 2h. Blood samples were collected every 10 min and used for ionic calcium and PTH measurements. During the basal period, an additional sample was collected for the determination of osteocalcin, FSH, and estradiol. A sample of early morning second voided urine was collected for analysis of deoxypiridinoline and creatinine as well as bone mass density (BMD) was determined by dual X-ray energy absorptiometry (DEXA). RESULTS: The aged patients presented lower femoral BMD (Y=0.860 g/cm(2) vs. M=0.690 g/cm(2), p<0.01), with four of them having a T score lower than -2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar in both groups. However, among aged volunteers, the rise in PTH levels was higher for subjects with normal bone mass (NM: peak=236 pg/ml) than for subjects with osteoporosis (OM: peak=134.4 pg/ml). CONCLUSIONS: The present results suggest that PTH can have a modulating effect on the rate of bone loss during late menopause.

Evidence for restoration of hepatic glucose processing in type I diabetes mellitus.

The role of muscle in the processing of dietary carbohydrate in nine type I diabetic patients was assessed using combined forearm-indirect calorimetry-glucose meal (100 g) studies performed before and after 72 h of artificial beta-cell directed insulin therapy. On conventional insulin therapy, initially elevated arterial glucose concentrations rose markedly, free insulin increased slightly, and the respiratory quotient (R.Q.) did not change during the study. The forearm glucose extraction rate increased significantly over basal at 60 min. After 72 h of artificial beta-cell therapy and while still on the instrument, arterial glucose increased moderately, and free insulin levels increased markedly. The R.Q. increased significantly at 60 and 120 min. The forearm glucose extraction rate increased significantly over basal at 30 and 60 min. Importantly, forearm glucose extraction rates did not differ during the two studies at each of the measured time points. These observations demonstrate that conventional insulin therapy is effective in facilitating glucose entry into muscle. In addition, they suggest that the marked improvement in glucose processing exhibited by type I diabetic patients after 72 h of artificial beta-cell therapy is primarily attributable to the liver. Finally, the data strongly imply that the primary clinical objective of insulin therapy in type I diabetes mellitus should be reactivation of the hepatic component of the glucose disposal system.

Impaired cytokine production by peripheral blood mononuclear cells in type 1 diabetic patients.

AIMS: The objective of the present investigation was to study the production of IL-1, IL-6, IL-10, IFNgamma and TNFalpha in cultures of peripheral blood mononuclear cells (PBMC) taken from type 1 diabetic patients with inadequate metabolic control. METHODS: Seventeen type 1 diabetic patients and a gender- and age-matched group of 17 healthy individuals were studied. PBMC cultures were stimulated with phytohemagglutinin (PHA; 20 microg/ml) and lipopolysaccharide (LPS; 10 microg/ml), and enzyme immunoassay (Elisa) was used to measure IL-1, IL-6, IL-10, IFNgamma and TNFalpha in the cell-culture supernatants. RESULTS: IFNgamma levels in PHA-stimulated cultures were lower in the type 1 diabetics than in the non-diabetic controls (P<0.0001) while, in contrast, IL-10 levels were increased in the PHA-stimulated culture supernatants of the diabetics compared with the controls (P<0.0001). In addition, supernatant levels of the cytokines IL-1, IL-6 and TNFalpha released in the presence of LPS in the cell cultures from the diabetic patients were significantly lower than in the non-diabetic subjects (P<0.0001, P<0.0001 and P<0.03, respectively). CONCLUSIONS: The impaired production of IL-1, IL-6, TNFalpha and IFNgamma, and the increased production of IL-10, in PBMC cultures from type 1 diabetics with inadequate metabolic control compared with healthy subjects may be an indication of a deficiency in mononuclear cell activation and, consequently, a deficient immune cellular adaptive response that, in turn, may be the cause of the increased incidence of infections in people with type 1 diabetes.

Lack of relationship between glycemic control and bone mineral density in type 2 diabetes mellitus.

We assessed the effect of chronic hyperglycemia on bone mineral density (BMD) and bone remodeling in patients with type 2 diabetes mellitus. We investigated 42 patients with type 2 diabetes under stable control for at least 1 year, 22 of them with good metabolic control (GMC: mean age = 48.8 +/- 1.5 years, 11 females) and 20 with poor metabolic control (PMC: mean age = 50.2 +/- 1.2 years, 8 females), and 24 normal control individuals (CG: mean age = 46.5 +/- 1.1 years, 14 females). We determined BMD in the femoral neck and at the L2-L4 level (DEXA) and serum levels of glucose, total glycated hemoglobin (HbA1), total and ionic calcium, phosphorus, alkaline phosphatase, follicle-stimulating hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OH-D), insulin-like growth factor I (IGFI), osteocalcin, procollagen type I C propeptide, as well as urinary levels of deoxypyridinoline and creatinine. HbA1 levels were significantly higher in PMC patients (12.5 +/- 0.6 vs 7.45 +/- 0.2% for GMC and 6.3 +/- 0.9% for CG; P < 0.05). There was no difference in 25-OH-D, iPTH or IGFI levels between the three groups. BMD values at L2-L4 (CG = 1.068 +/- 0.02 vs GMC = 1.170 +/- 0.03 vs PMC = 1.084 +/- 0.02 g/cm(2)) and in the femoral neck (CG = 0.898 +/- 0.03 vs GMC = 0.929 +/- 0.03 vs PMC = 0.914 +/- 0.03 g/cm(2)) were similar for all groups. PMC presented significantly lower osteocalcin levels than the other two groups, whereas no significant difference in urinary deoxypyridine was observed between groups. The present results demonstrate that hyperglycemia is not associated with increased bone resorption in type 2 diabetes mellitus and that BMD is not altered in type 2 diabetes mellitus.

Effect of metabolic control on interferon-gamma and interleukin-10 production by peripheral blood mononuclear cells from type 1 and type 2 diabetic patients.

The objective of the present study was to evaluate the production of cytokines, interferon-gamma (INF-gamma) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-gamma and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-gamma levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-gamma and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-gamma and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.

Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling.

Data about the impact of bariatric surgery (BS) and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD), bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16). The data were compared to those obtained for women of normal weight (CG, N = 11) and for obese women (OG, N = 12). Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I) and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 +/- 62 vs OG = 230 +/- 37 vs OGg = 128 +/- 19 ng/mL) were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

Aliskiren effect on non-alcoholic steatohepatitis in metabolic syndrome.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is highly associated with metabolic syndrome, a major cause of morbidity in the globalized society. The renin-angiotensin system (RAS) influences hepatic fatty acid metabolism, inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related NASH. METHODS: C57BL/6 male mice (n = 45) were divided into three groups: controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for 5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for the final 2 weeks. Glycemic and insulin levels, hepatic lipid profile, histological parameters and inflammatory protein expression were analyzed. RESULTS: Aliskiren normalized plasma glucose and insulin levels, reduced cholesterol, triglycerides and total fat accumulation in liver and diminished hepatic injury, steatosis and fibrosis. These results could be explained by the ability of aliskiren to block angiotensin-II, lowering oxidative stress and inflammation in liver. Also, it exhibited a beneficial effect in increasing insulin sensitivity. CONCLUSION: These findings support the use of aliskiren in the treatment of metabolic syndrome underlying conditions. However, clinical studies are indispensable to test its effectiveness in the treatment of patients with metabolic syndrome.

Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting beta-cell regeneration.

Type 1 diabetes mellitus results from a cell-mediated autoimmune attack against pancreatic beta-cells. Traditional treatments involve numerous daily insulin dosages/injections and rigorous glucose control. Many efforts toward the identification of beta-cell precursors have been made not only with the aim of understanding the physiology of islet regeneration, but also as an alternative way to produce beta-cells to be used in protocols of islet transplantation. In this review, we summarize the most recent studies related to precursor cells implicated in the regeneration process. These include embryonic stem cells, pancreas-derived multipotent precursors, pancreatic ductal cells, hematopoietic stem cells, mesenchymal stem cells, hepatic oval cells, and mature beta-cells. There is controversial evidence of the potential of these cell sources to regenerate beta-cell mass in diabetic patients. However, clinical trials using embryonic stem cells, umbilical cord blood or adult bone marrow stem cells are under way. The results of various immunosuppressive regimens aiming at blocking autoimmunity against pancreatic beta-cells and promoting beta-cell preservation are also analyzed. Most of these regimens provide transient and partial effect on insulin requirements, but new regimens are beginning to be tested. Our own clinical trial combines a high dose immunosuppression with mobilized peripheral blood hematopoietic stem cell transplantation in early-onset type 1 diabetes mellitus.

Health in early adulthood: the contribution of the 1978/79 Ribeirão Preto birth cohort.

The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with alpha = 0.05. Obesity was similar among men and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%). Weight deficit was higher among women than among men (8.6 and 2.6%). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%), hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.

Restoration of glucose homeostasis in insulin-dependent diabetic subjects. An inducible process.

To assess the change in glucose handling capability of diabetic patients regulated with an artificial beta-cell, five insulin-dependent diabetic subjects were challenged with a 100-g glucose meal while on conventional (*single or split mixed insulin injections) therapy and again after 72 h on an artificial beta-cell unit. It was determined that while receiving conventional therapy, the diabetic patient's capacity to oxidize glucose was severely impaired. In addition, glucose storage was markedly reduced. After 72 h on the artificial beta-cell unit, the diabetic patient's capacity to oxidize glucose following the ingestion of the glucose meal significantly exceeded that of the control group, and glucose storage returned to normal. Since the above study did not reveal the amount of time on the artificial beta-cell required to restore the glucose processing capability of the diabetic patients to normal, their response to a mixed test meal ingested at noon was monitored while they were on conventional insulin therapy and during four consecutive days that they were on the artificial beta-cell. This inquiry revealed a gradual increase in their capacity to oxidize carbohydrate in response to the test meal. In contrast, their ability to store carbohydrate was normalized within 24 h following initiation of artificial beta-cell therapy. These studies clearly reveal that the conventionally treated diabetic patient's capacity to both oxidize and store carbohydrate is severely impaired. Both functions can be restored to normal by the use of the artificial beta-cell for 48-72 h. Most importantly, the gradual improvement in carbohydrate oxidation with respect to the daily mixed meal challenge suggests that it is an "inducible" process which requires at least 2-3 days to accomplish. Since the ability to both oxidize and store incoming carbohydrate is essential for glucose homeostasis, these observations may have significant implications for the care of diabetic patients.

[Skin lesions in diabetic patients]. / Dermatoses em pacientes com diabetes mellitus.

OBJECTIVE: It is yet unknown the relationship between diabetes and determinants or triggering factors of skin lesions in diabetic patients. The purpose of the present study was to investigate the presence of unreported skin lesions in diabetic patients and their relationship with metabolic control of diabetes. METHODS: A total of 403 diabetic patients, 31% type 1 and 69% type 2, underwent dermatological examination in an outpatient clinic of a university hospital. The endocrine-metabolic evaluation was carried out by an endocrinologist followed by the dermatological evaluation by a dermatologist. The metabolic control of 136 patients was evaluated using glycated hemoglobin. RESULTS: High number of dermophytosis (82.6%) followed by different types of skin lesions such as acne and actinic degeneration (66.7%), pyoderma (5%), cutaneous tumors (3%) and necrobiosis lipoidic (1%) were found. Among the most common skin lesions in diabetic patients, confirmed by histopathology, there were seen necrobiosis lipoidic (2 cases, 0.4%), diabetic dermopathy (5 cases, 1.2%) and foot ulcerations (3 cases, 0.7%). Glycated hemoglobin was 7.2% in both type 1 and 2 patients with adequate metabolic control and 11.9% and 12.7% in type 1 and 2 diabetic patients, respectively, with inadequate metabolic controls. A higher prevalence of dermatophytoses was seen in the both groups with inadequate metabolic control. CONCLUSIONS: The results showed a high prevalence of skin lesions in diabetic patients, especially dermatophytoses. Thus, poor metabolic control of diabetes increases patient's susceptibility to skin infections.

Restoration of fuel homeostasis in IDDM patients during pregnancy by an open-loop insulin infusion system.

OBJECTIVE: To characterize the effects of subcutaneous insulin pump therapy on the metabolic response (CHO and lipid oxidation, and nonoxidative glucose metabolism) to a glucose challenge of diabetic women at early pregnancy. RESEARCH DESIGN AND METHODS: Seven nondiabetic and seven IDDM pregnant patients on insulin pump therapy were studied at the first trimester. Fuel oxidation rates were determined by indirect calorimetry, and blood levels of substrates and hormones were measured before and for 2 h after ingestion of a 50 g oral glucose load. RESULTS: The increments in npRQ and CHO oxidation rates after the glucose meals in the diabetic women on insulin pump therapy were similar to those in the normal subjects. The glucose disposal data during the 2 h of the studies revealed that the amounts of oxidative and nonoxidative glucose utilization in the control subjects and in the IDDM patients on insulin pump therapy did not show significant differences. CONCLUSIONS: This investigation demonstrated that the treatment of IDDM patients during early pregnancy by an open-loop insulin infusion system is sufficient to normalize their glucose-processing capability with respect to cellular oxidative and nonoxidative glucose metabolism in response to an oral glucose challenge, but some abnormalities in their blood profiles of glucose, lactate, and pyruvate persisted.

Peripheral glucose metabolism in acromegaly.

The present study was designed to determine the effect of chronic GH excess on forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Nine normal subjects and 10 nondiabetic acromegalic patients (5 of them with normal glucose tolerance) were studied after an overnight fast (12-14 h) and for 3 h after the ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Decreased forearm glucose uptake was observed in the acromegalic patients compared to that in the normal subjects (380 +/- 84 vs. 709 +/- 56 mumol/100 mL forearm.3 h) with diminished nonoxidative glucose metabolism (262 +/- 81 vs. 572 +/- 53 mumol/100 mL forearm.3 h). The acromegalics with normal glucose tolerance also showed decreased forearm glucose uptake and nonoxidative glucose metabolism compared to normal subjects (271 +/- 124 vs. 709 +/- 56 and 133 +/- 110 vs. 572 +/- 53 mumol/100 mL forearm.3 h, respectively). Muscle glucose oxidation did not differ significantly in normal subjects, the entire group of acromegalic patients, and the acromegalics with normal glucose tolerance (137 +/- 18 vs. 118 +/- 22 vs. 138 +/- 34 mumol/100 mL forearm.3 h, respectively). Serum FFA levels and lipid oxidation rates were similar in the normal subjects and the acromegalic patients, and declined in a similar fashion after glucose ingestion. Insulin levels were significantly higher in acromegalic patients than in normal subjects before and after glucose loading. In conclusion, this study showed that the insulin resistance occurring in the presence of chronic GH excess is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism, which are early derangements because they are also observed in acromegalic patients with normal glucose tolerance.

Peripheral glucose metabolism in human hyperthyroidism.

The present study was designed to determine the effect of spontaneous hyperthyroidism on the forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Ten normal subjects and 11 hyperthyroid patients were studied after an overnight fast (12-14 h) and for 3 h after ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Increased forearm glucose uptake was observed in the hyperthyroid patients compared to that in the normal subjects (1286 +/- 212 vs. 677 +/- 88 mumol/100 mL forearm.3 h) with enhanced glucose oxidation (443 +/- 40 vs. 147 +/- 29 mumol/100 mL forearm.3 h). Nonoxidative glucose metabolism was also greater in hyperthyroid patients than in normal subjects (842 +/- 234 vs. 529 +/- 90 mumol/100 mL forearm.3 h). Basal serum FFA levels were significantly higher in hyperthyroid than in normal subjects (0.252 +/- 0.025 vs. 0.182 +/- 0.022 g/L), as were the basal lipid oxidation rates in the forearm muscles of the thyrotoxic individuals (0.290 +/- 0.066 vs. 0.088 +/- 0.016 mg/100 mL forearm.min). After glucose ingestion, serum FFA levels and lipid oxidation rates declined significantly to equivalent values in both groups of subjects, and the similar basal insulin concentrations increased to significantly higher levels in the hyperthyroid patients. In conclusion, spontaneous human hyperthyroidism increases glucose uptake by the forearm muscles in the postabsorptive state and during an oral glucose challenge, with augmented fluxes of glucose through the oxidative and nonoxidative pathways.

Treatment of diabetic gastroparesis with oral clonidine.

BACKGROUND/AIMS: Clonidine, a specific alpha-2-adrenergic receptor agonist, has been suggested to improve symptoms of gastroparesis in diabetics with diarrhoea. The aim of this study was to investigate the effects of clonidine on gastric emptying and symptoms suggestive of gastroparesis in patients with longstanding diabetes mellitus and evidence of autonomic neuropathy. METHODS: Six diabetics with chronic, refractory symptoms of bloating, nausea and vomiting were studied. Gastric emptying of a liquid nutrient meal (250 mL; 430 kcal) was evaluated by scintigraphy and symptoms were scored. Patients were treated with clonidine (median dose: 0.3 mg/day) for 2-12 weeks (median: 4 weeks), after which symptoms and gastric emptying were re-evaluated. Treatment was then sustained for a median follow-up period of 7 weeks (range: 2-56 weeks). RESULTS: Gastric emptying half-time values in diabetic patients ranged from 16 to 180 min (median: 100 min) and four patients had abnormally delayed emptying before treatment. In all patients, half-time values decreased during treatment (median: 35 min; range: 14-106 min, P < 0.025 vs. pre-treatment values) and in three of the four patients with abnormal gastric retention, half-time values returned to the normal range. During clonidine treatment, a substantial decrease in the score for symptoms was observed (median and range: 7.5; 2-9 vs. 0; 0-9). In four patients, symptoms virtually disappeared, an effect that was maintained throughout follow-up (6-56 weeks). CONCLUSIONS: These findings suggest that impairment of adrenergic influences on gastrointestinal motility control may play a role in the pathophysiology of diabetic gastroparesis and that clonidine may be a useful alternative for treating patients with this condition.

Cholinergic bronchomotor tone and airway caliber in insulin-dependent diabetes mellitus.

It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the present study, we assessed the cholinergic bronchomotor tone in 34 insulin-dependent diabetic patients and in a control group of 32 healthy subjects (group C). As an index of the intensity of cholinergic tone to the airways, we measured the increase in specific airway conductance (Gaw/VL) induced by aerosol administration of atropine sulfate. In all of the patients and normal individuals the autonomic cardiovascular activity was also evaluated by the tilting test and by the magnitude of the respiratory sinus arrhythmia (RSA). In 19 patients without symptoms of autonomic neuropathy (AN) (group D-1), the autonomic cardiovascular activity was comparable to that of group C. The other 15 patients presented with at least one symptom of AN and a depressed heart rate (HR) control when submitted to the tests of autonomic activity (group D-2). Before atropine administration, Gaw/VL was significantly higher (p less than 0.05) in group D-2 (2.48 +/- 0.12 s-1.kPa-1 [mean +/- SE]) than in group D-1 (2.11 +/- 0.10 s-1.kPa-1). Aerosol atropine caused a significant increase (p less than 0.001) in airway caliber in all three groups; however, the increase in Gaw/VL was significantly lower in group D-2 (0.26 +/- 0.05 s-1.kPa-1) when compared with group D-1 (0.63 +/- 0.09 s-1.kPa-1; p less than 0.01) and group C (0.67 +/- 0.06 s-1.kPa-1; p less than 0.001). A weak but significant (p less than 0.02) correlation was observed between the increases in Gaw/VL provoked by atropine and the magnitude of RSA. Our findings suggest that the reduction in parasympathetic bronchomotor tone may cause an increase in basal airway caliber in diabetic patients with AN, compared to patients without AN.

HLA-DRB1, DQB1, and DQA1 allele profile in Brazilian patients with type 1 diabetes mellitus.

HLA class II profile was evaluated in 64 Brazilian patients presenting with type 1 diabetes mellitus. Although the Brazilian population is highly miscegenated, HLA-DRB1*301, DRB1*04, DQB1*0302, and DQB1*0201 alleles, which are associated with the development of type 1 diabetes in several Western populations, were also overrepresented in Brazilian patients. In addition to HLA-DRB1*15 and DQB1*0602 alleles, DRB1*11, DRB1*13, and DQA1*01 allele groups were associated with protection against the development of type 1 diabetes in Brazilian patients.

Lipolysis and the antilipolytic effect of insulin in adipocytes from rats adapted to a high-protein diet.

Free fatty acid (FFA) mobilization during fasting was investigated in rats fed a high-protein, carbohydrate-free (HP) diet (70% casein, 8% fat, wt/wt) or a balanced diet (66% carbohydrate, 17% casein, 8% fat) for 30 to 40 days. In vivo, rats on the HP diet showed reduced rates of plasma FFA increase during fasting. Their blood sugar remained unchanged and was higher than that of control rats 24 hours after removal of food. In the fed state, serum insulin levels were smaller in HP-fed rats but did not differ significantly in the two experimental groups during fasting. In vitro, the rates of glycerol and FFA release by epididymal fat pads obtained from fasted rats were similar in rats consuming the HP diet. Fat cells isolated from rats on the HP diet also had reduced rates of basal lipolysis. Furthermore, they showed a significant increase in responsiveness to the lipolytic action of noradrenaline and an increase in both sensitivity and responsiveness to the inhibitory effect of insulin on noradrenaline-stimulated lipolysis. Adipocytes from HP-fed and control rats had mean diameters of 51 and 60 mu, respectively, and estimated average volumes of 90 and 142 pL. On the basis of existing data on the correlation between size and lipolytic activity of fat cells, the smaller size of the adipocytes from HP-fed rats might account for the lower rate of basal lipolysis but not for the increased response to the hormones. The increased sensitivity of fat cells to the antilipolytic action of insulin may have been an important factor in the reduced lipomobilization during fasting in rats under the high-protein regimen.